Brain inositol monophosphatase identified as a galactose 1-phosphatase.
During the course of our analysis of myo-inositol monophosphatase (IMPase), a key enzyme of brain inositol signaling, we found it also hydrolyzes galactose 1-phosphate (Gal 1-P), an intermediate of galactose metabolism. Electrophoretically homogeneous IMPase was prepared from three different sources: (i) bovine brain, (ii) rat brain, and (iii) human brain (recombinant), which demonstrated similar ability to hydrolyze inositol monophosphates and galactose 1-phosphate. The ability of IMPase to use both inositol 1-phosphates and galactose 1-phosphate equally as substrates is of considerable importance in determining lithium's mechanism of action. Our current results suggest that during lithium therapy, both galactose and inositol metabolic pathways can be simultaneously modulated through lithium inhibition of IMPase. Enzyme studies with Mg2+ ions as activators and with Li+, Ca2+, Mn2+, Ba2+ ions as inhibitors demonstrate that IMPase is a single enzyme possessing the ability to hydrolyze both inositol monophosphates and Gal-1-P with equal efficiency. In addition, gel-filtration chromatographic analysis demonstrated that IMPase and galactose 1-phosphatase activities co-purify in our electrophoretically homogeneous enzyme preparations. Our results indicate that lithium inhibition of IMPases at clinically relevant concentrations, may modulate both inositol and galactose metabolism, and identifies yet another carbohydrate pathway utilizing IMPase.
Parthasarathy
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Molecular Neuroscience Laboratory, Mental Health and Behavioral Science Service, Department of Veterans Affairs Medical Center (116), Louisville, KY 40206, USA.
Parthasarathy
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L
Vadnal
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D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000201:enzymology*; D002417:Cattle; D002850:Chromatography, Gel; D005690:Galactose / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D008969:Molecular Sequence Data; D010744:Phosphoric Monoester Hydrolases / Q000032:analysis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology
C069910:galactose-1-phosphatase; D010744:Phosphoric Monoester Hydrolases; C021822:myo-inositol-1 (or 4)-monophosphatase; D005690:Galactose